Project Summary: Dr. James Lord, M.D., Ph.D., is a motivated senior gastroenterology fellow with a strong background in basic immunology research. His immediate career plans involve understanding how regulatory T cells (Tregs) fail to prevent inflammation in inflammatory bowel disease. He proposes to study dendritic cells (DC) in the surgically resected bowels of patients with IBD, to determine if and how certain subtypes of DC prevent Tregs from inhibiting other T cells. He plans to identify the surface receptors and soluble cytokines produced by these DC, and determine if these may impair Treg function. He also will determine if DC indirectly impair Treg function by altering the differentiation of other T cells to become less responsive to Treg-mediated inhibition. This research will be performed under the mentorship of Steven Ziegler, a well-established Treg biologist. The Ziegler lab is well equipped for molecular and cellular immunology research, and exists within the Benaroya Research Institute (BRI). The BRI is an academic research facility dedicated to the study of autoimmune and chronic inflammatory conditions, and as such contains many material and human resources vital to the study of human immunology. The BRI is itself affiliated with the University of Washington, which represents a large, prestigious and vibrant reseach [sic] community. The BRI is also affiliated with, and recruits study subjects from, the Virginia Mason Medical Center, which is one of the busiest tertiary referral centers for IBD in the Pacific Northwest. Dr. Lord's long-term career plans involve building upon his dual backgrounds in clinical gastroenterology and basic immunology to forge a link between the large clinical gastroenterology community and the strong basic immunology research community currently present in Seattle. His career development plan outlines a curriculum of research, didactic coursework, and local and national conference attendance, designed to foster his maturation into a successful translational researcher. Relevance to Public Health: Despite significant advances in our understanding of the immune system, IBD remains incurable, poorly understood, and both challenging and expensive to treat. If the proposed experiments reveal a fundamental mechanism by which IBD occurs, they may not only reveal new potential treatment strategies for tomorrow, but also allow physicians to better target the treatments they have today.